Progress in CYP Enzymes Mechanisms of Induction and Its Applications

Zhanxu Meng

2024

Abstract

Cytochrome P450 (CYP) enzymes are pivotal in the metabolic processing of drugs, and their modulation via induction pathways plays an important role in the therapeutic efficacy, safety, and drug interaction profile. This comprehensive review delineates three focal points concerning CYP enzyme induction. The first domain scrutinizes the accuracy of in vitro methodologies-predominantly cryopreserved primary human hepatocytes (PHH) and Human HepaRG cells-in forecasting the in vivo dynamics of CYP enzymes. The second segment elucidates novel induction paradigms, highlighting the enduring induction of CYP1A enzymes via 3-methylcholanthrene (MC) in murine models and the atypical induction pathways that involve YAP/TEAD perturbation and consequent hepatocyte dedifferentiation. The terminal section evaluates the application of these findings in clinical settings, discussing the kinetic profiling of CYP3A modulation and the transposition of in vitro CYP repression to actual drug-drug interaction scenarios. The synthesis of these facets contributes to an enriched understanding of CYP induction mechanisms and their ramifications for drug discovery and tailored therapeutic approaches. Furthermore, the appraisal accentuates the reliability and pertinence of cryopreserved PHH and HepaRG cells as in vitro proxies for human CYP enzyme induction studies, potentially informing regulatory risk evaluation and elucidating drug metabolism and nuclear receptor-mediated regulatory anomalies in biochemical pathways.

Paper Citation

in Harvard Style

Meng Z. (2024). Progress in CYP Enzymes Mechanisms of Induction and Its Applications. In Proceedings of the 2nd International Conference on Renewable Energy and Ecosystem - Volume 1: ICREE; ISBN 978-989-758-776-4, SciTePress, pages 76-86. DOI: 10.5220/0013846300004914

in Bibtex Style

@conference{icree24,
author={Zhanxu Meng},
title={Progress in CYP Enzymes Mechanisms of Induction and Its Applications},
booktitle={Proceedings of the 2nd International Conference on Renewable Energy and Ecosystem - Volume 1: ICREE},
year={2024},
pages={76-86},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0013846300004914},
isbn={978-989-758-776-4},
}

in EndNote Style

TY - CONF

JO - Proceedings of the 2nd International Conference on Renewable Energy and Ecosystem - Volume 1: ICREE
TI - Progress in CYP Enzymes Mechanisms of Induction and Its Applications
SN - 978-989-758-776-4
AU - Meng Z.
PY - 2024
SP - 76
EP - 86
DO - 10.5220/0013846300004914
PB - SciTePress